Abstract
Objectives
To identify respiratory comorbidities associated with a high risk of developing respiratory failure in subjects with psoriasis.
Methods
This was a cross-sectional analysis of data from subjects enrolled in the UK Biobank cohort. All diagnoses were self-reported. The risk of each respiratory comorbidity was compared by logistic regression models adjusting for age, sex, weight, diabetes mellitus, and smoking history; the risk of comorbid respiratory failure for each pulmonary comorbidity was also compared.
Results
Of the 472,782 Caucasian subjects in the database, 3,285 self-reported a diagnosis of psoriasis. More men and smokers reported psoriasis and were older, had higher weight and body mass index, and lower pulmonary function than non-psoriatic subjects. Those with psoriasis were at significantly higher risk for multiple pulmonary comorbidities compared to those without psoriasis. Furthermore, those with psoriasis had a higher risk for respiratory failure accompanied by asthma and airflow limitation than non-psoriatic subjects.
Conclusions
Subjects with psoriasis and pulmonary comorbidities, such as asthma and airflow limitation, are at increased risk for respiratory failure. Common immunopathological links implicating a ‘skin-lung axis’ may underlie psoriasis and pulmonary comorbidities.
Introduction
Psoriasis is a common, systemic, inflammatory disease, that affects approximately 125 million individuals globally. 1 The skin lesions are characterized primarily by distinct reddened, white scaly skin plaques with hyperproliferation of keratinocytes and infiltration of inflammatory cells including T cells, neutrophils, and macrophages. 2
While psoriasis typically affects skin, it has been associated with a number of systemic manifestations including, respiratory disease, arthritis, cardiovascular diseases, diabetes, and depression. 1 Important comorbidities associated with psoriasis may lead to a substantial economic burden and affect the quality and/or quantity of life for affected patients. 1 Indeed, a retrospective study that included 56,406 psoriatic patients from a US database, reported that those with comorbidities used more healthcare resources, and had higher direct and indirect costs due to short-term disability compared with those without comorbidities. 3 Moreover, despite progress in medical management, patients with psoriasis, have a high mortality risk for cancer, circulatory diseases, and respiratory diseases. 4
In terms of respiratory comorbidities, psoriasis has been found to be associated with an increased incidence of asthma, 5 chronic obstructive pulmonary disease (COPD), 6 lung cancer, 7 pulmonary hypertension (PH), 8 and interstitial lung disease (ILD). 9 Psoriasis is also associated with acute diseases including pulmonary embolism 10 and respiratory infections. 11 While respiratory comorbidities will influence patients’ survival, it remains unclear which respiratory comorbidities will have greatest impact on the clinical course of the disease including mortality. Using data from a large-population-based database, we aimed to identify respiratory comorbidities associated with a high risk of developing respiratory failure in subjects with psoriasis.
Methods
For this cross-sectional study, data were obtained from the UK Biobank, a population-based cohort of approximately 500,000 participants who were recruited between 2006 and 2010. 12 The database was established to investigate genetic and nongenetic determinants of disease. Participants were aged 40–69 years and were enrolled throughout the UK from a variety of settings to provide heterogeneity in terms of socioeconomic status and ethnicity. Participants regularly provided blood, urine, and saliva samples and completed questionnaires, interviews, in addition to undertaking physical and functional measures.
The prevalence of psoriasis has been estimated to be 4.6% in the USA and 4.7% in Canada, but <1% in African Americans. 13 Therefore, because the majority of participants in the UK Biobank were Caucasian (>90%) we limited the current analysis to Caucasians. The diagnosis of psoriasis, respiratory comorbidities and smoking history were based on subject self-report. ‘Ever smoker’ was defined by current tobacco smoking (most days/occasionally) or past tobacco smoking (most days/ occasionally/ tried once or twice). We calculated forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and defined airflow limitation as FEV1/FVC <70%. We extracted diseases using ICD-10 codes; E08-13, diabetes mellitus; M07 and L40, psoriasis; J45, asthma; J43, emphysema; J47, bronchiectasis; I27, PH; J84, ILD; J10, J11, J12, C34, lung cancer; J96, respiratory failure.
The current analysis was exempt from ethics approval because it was performed on clinical data from a database and data were anonymized.
Statistical analysis
The analysis was performed using Microsoft Excel and Stata (StataCorp LLC. TX, USA) and P < 0.05 was considered statistically significant. Baseline characteristics were compared using χ2 tests for categorical variables and t-tests for continuous variables. The risk of each respiratory comorbidity in participants with or without psoriasis was compared using an adjusted odds ratio (OR) in separate logistic regression models. These models were adjusted for age (as a continuous variable), sex (male or female), and smoking history (ever smoked or not). The risk of comorbid respiratory failure for each pulmonary comorbidity was compared between participants with and without psoriasis using OR.
Results
Among the 472,782 Caucasian participants, 3,285 (0.7%) self-reported a diagnosis of psoriasis. Compared with non-psoriatic subjects, those with psoriasis were older and included more males and ‘ever smokers’. In addition, their weight and body mass index were higher than non-psoriatic subjects but their pulmonary function was lower (Table 1).
Baseline characteristics.
Data are expressed as, mean ± standard deviation, n, or n (%)
Abbreviations: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ns, not statistically significant.
We compared the risk of each respiratory comorbidity between subjects with and without psoriasis using logistic regression analysis. In the adjusted analysis for age, sex, weight, diagnosis of diabetes mellitus, and smoking history, by comparison with non-psoriatic subjects, the presence of psoriasis was associated with a statistically significantly higher prevalence of asthma (OR 1.89), emphysema (OR 2.54), bronchiectasis (OR 2.35), airflow limitation (OR 1.22), PH (OR 2.28), ILD (OR 2.51), and lung cancer (OR 1.58) (Table 2).
Risk of pulmonary comorbidities in psoriatic and non-psoriatic participants.
Data are expressed as n, or n (%).
Adjusted for age, sex, weight, diabetes mellitus and smoking history.
Abbreviations: OR, odds ratio; CI, confidence interval; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.
The risk of comorbid respiratory failure for each pulmonary comorbidity was compared between subjects with and without psoriasis. Psoriatic subjects with asthma (OR 3.07 [95% CI 2.13–4.43], P < 0.001), and airflow limitation (OR 2.87 [1.84–4.47], P < 0.001) had a statistically significantly higher risk for comorbid respiratory failure compared to non-psoriatic subjects (Table 3).
Risk of comorbid respiratory failure in psoriatic or non-psoriatic participants with a pulmonary comorbidity.
Data are expressed as n (%).
Abbreviations: OR; odds ratio, CI; confidence interval, FEV1; forced expiratory volume in 1 second, FVC; forced vital capacity; ns, not statistically significant.
Discussion
Consistent with findings from other studies, we found that subjects with psoriasis had a significantly greater risk for chronic pulmonary comorbidities including asthma, PH, ILD, and lung cancer compared with non-psoriatic subjects.5,7–9 In addition, we observed that subjects with psoriasis had a greater risk for emphysema and bronchiectasis compared with non-psoriatic subjects. These findings are in-line with previous studies that have shown that psoriatic patients have a high risk of developing COPD 6 . However, although we found asthma and airflow limitation in the psoriatic subjects were significantly associated with comorbid respiratory failure, emphysema and bronchiectasis were not associated.
Psoriasis is a chronic inflammatory disease complicated by an activated immune process. 1 Dendritic cells (Tc17 and Th17), and T1 lymphocytes exert a key role in the pathophysiology of psoriasis.14,15 The complexity of the pathophysiology of psoriasis is influenced by various factors such as genetic predisposition, and environmental, habitual, or nutritional status; smoking, drinking, and obesity, have been identified as risk factors for developing psoriasis. 16 In addition, it has been suggested that psoriasis occurs as a result of an interaction between genetic factors of the host and environmental triggers. 16 However, smoking, one of the important risk factors, can modify risk estimates for genetic markers. 17
Multiple genetic risk loci for susceptibility to psoriasis have been identified and shown to be associated with inflammatory pathways, regulating interleukin (IL)-23/IL-17, nuclear factor kappa B (NF-kB), and Type 1 interferon signaling.18–22 These inflammatory pathways are also important in respiratory diseases; therefore, the two diseases share common inflammatory pathogenic pathways. For example, Th1 and Th17 T lymphocytes play an important role in the inflammatory process of COPD or non-type2 asthma.23,24 A combined analysis of genome-wide association studies (GWAS) from large COPD case-control studies (i.e., COPDGene, GenKOLS, and ECLIPSE) identified several genes associated with CD4 T cell response. 25 GWAS of lung function identified that the Th1 pathway genes modify lung function in asthmatic subjects. 26 Moreover, an experimental mouse model using imiquimod and cockroach extract showed that psoriatic inflammation exacerbates Th2/Th17 allergic inflammation through the IL-23/STAT-3 pathway. 27 As assessed by fractional exhaled nitrous oxide, clinically, psoriatic patients have increased airway inflammation, and comorbid psoriatic arthritis has been found to be associated with exacerbated airway inflammation.28,29 In addition, dermatological treatment of psoriasis has been shown to alleviate neutrophilic airway inflammation. 30 Common immunopathological links implicating a ‘skin-lung axis’ may underlie psoriasis and pulmonary comorbidities.
Our study had some limitations. For example, all diseases were self-reported and so there is a possibility of recall bias. Selection bias and misclassification bias may have also occurred. In addition, we lacked data on severity of the diseases, causes of respiratory failure, and treatments. Therefore, our results may have been influenced by other confounders such as medications (e.g., immunosuppressants). Indeed, patients with severe disease are reported to have an increased risk for infectious diseases requiring hospitalizations, suggesting that systemic psoriatic drugs may increase a patient's susceptibility to infectious disease. 31 To address these limitations, further validation work will be necessary using large samples and different populations.
In conclusion, psoriasis is now recognized as a systemic inflammatory disease and signs of inflammation can be detected at sites outside the skin. 1 We found that psoriatic subjects with pulmonary comorbidities, such as asthma and airflow limitation, may be predisposed to the development of respiratory failure. Therefore, physicians need to be aware of these pulmonary comorbidities because they could impair the quality of life and survival of patients with psoriasis.
Footnotes
Acknowledgment
This research has been conducted using the UK Biobank Resource under Application Number 60327.
Declaration of conflicting interests
The authors declare that there are no conflicts of interest.
Funding
This manuscript was supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research, and Development by a Merit Review award CX000105 (T.N.). This work was also supported by American Heart Association (T.N.); NIH grants R01HL149719 to T.N.
